For the diagnosis and prophylaxis of diabetes mellitus, the importance of periodically monitoring blood glucose levels is increasingly emphasized. Nowadays, strip-type biosensors designed to be used in hand-held reading devices allow individuals to readily monitor glucose levels in the blood.
Many various commercialized biosensors measure the blood glucose content of blood samples using an electrochemical technique. The principle of the electrochemical technique is based on the following Reaction 1.Glucose+GOx-FAD→gluconic acid+GOx-FADH2 GOx-FADH2+Mox→GOx-FAD+Mred  [Reaction 1]
wherein, GOx represents glucose oxidase; GOx-FAD and GOx-FADH2 respectively represent an oxidized and a reduced state of glucose-associated FAD (flavin adenine dinucleotide), a cofactor required for the catalysis of glucose oxidase; and Mox and Mred denote the oxidized and reduced states, respectively, of an electron transfer mediator.
The electrochemical biosensor uses as electron transfer mediators organic electron transfer materials, such as ferrocenes or derivatives thereof, quinines or derivatives thereof, organic or inorganic materials containing transition metals (hexamine ruthenium, polymers containing osmium, potassium ferricyanide and the like), organic conducting salts, and viologens.
The principle by which blood glucose is measured using the biosensor is as follows.
Glucose in the blood is oxidized to gluconic acid by the catalytic activity of glucose oxidase, with the cofactor FAD reduced to FADH2. Then, the reduced cofactor FADH2 transfers electrons to the mediator, so that FADH2 returns to its oxidized state; that is, FAD and the mediator are reduced. The reduced mediator is diffused to the surface of the electrodes. The series of reaction cycles is driven by the anodic potential applied at the working electrode, and redox current proportional to the level of glucose is measured. Compared to biosensors based on colorimetry, electrochemical biosensors (that is, based on electrochemistry) have the advantages of not being influenced by the turbidity or color of the samples and allowing the use of wider range of samples, even cloudy ones, without pretreatment thereof.
Although this electrochemical biosensor is generally convenient when used to monitor and control the amount of blood glucose, its accuracy is greatly dependent on lot-to-lot variation between respective mass-produced lots in which the biosensors are produced. In order to eliminate such variation, most of the commercialized biosensors are designed such that a user directly inputs calibration curve information, which is predetermined at the factory, into a measuring device capable of reading the biosensor. However, this method inconveniences the user a great deal and causes the user to make input errors, thus leading to inaccurate results.
In order to solve this problem, a method by which the resistance of each electrode can be adjusted such that the variations in mass production is corrected (US20060144704A1), a method in which a connection to a resistor bank is made (WO2007011569A2), and a method by which information is read by varying resistance through the adjustment of the length or the thickness of each electrode (US20050279647A1) have been proposed. The methods proposed for the electrochemical biosensors are all based on a technique in which electrical variation is read. Furthermore, a method for distinguishing production lot information by reading the resistivity of a conductor marked on a strip using an electrical method (U.S. Pat. No. 4,714,874) has been proposed.
However, these methods function to accurately adjust resistance, and require a process of mass-producing the sensors first, measuring the statistical characteristics of the sensors, and post-processing the measured information again using a method of adjusting the resistance marked on the sensors. However, the process of accurately adjusting the resistance, marked in large quantities, through the post-processing is very inconvenient, and is difficult to use in practical applications.
Methods in which colored marks are used with a spectral system capable of discriminating colors to realize a colorimetric method (U.S. Pat. No. 3,907,503, U.S. Pat. No. 5,597,532, U.S. Pat. No. 6,168,957), and a method capable of reading bar codes (EP00075223B1, WO02088739A1) have been proposed. These methods using color or bar codes are favorable for a calorimetric method-based sensor using the spectrum system, but they have technical and economic difficulties when applied to a system using an electrochemical measurement mechanism. For example, the size and structure of the area where the electrochemical sensor strip is inserted into the measuring device for the purpose of electrical connection, that is, the connection space of the sensor strip, is very limited when constructing a device and circuit for spectroscopically identifying a structure into which the production lot information is input, which results in a great increase in system construction expense.
Furthermore, instead of the methods of marking the production lot information on the sensor strip, a method of recording information on a container or pack containing a sensor and allowing the information to be read by the measuring device has been proposed. However, this method also has a possibility of causing the user to make an error.
For conventional methods developed in order for users to measure the blood glucose levels thereof using disposable electrochemical biosensor strips without the need to manually input accurate calibration curve information about biosensors, which differs from one production lot to another into a measuring device, the sensors require a long period of time for the preparation thereof, and also require post-processing, in which errors are likely to be made.
Also, conventional devices for reading hue marks using a filter or a monochromator for the wavelength of a light source encounter great spatial limitations and pose problems in the construction of small-sized systems.
Thus, there is a need for a biosensor that has a mark which is simple and can be easily marked within a short time period, such as hue marks, which are convenient to print on a small area of a biosensor, or hole marks, which can be easily prepared simultaneously when the final press process for mass production is performed, thereby allowing the biosensor to be produced on a mass scale. Also, there is a need for a biosensor that has production lot information recorded on the mark through which the production lot information can be thus inputted to an insulation plate of the biosensor, so that when the biosensor is inserted into a measuring device, the production lot information is automatically identified without a mistake being made by a user, thus enabling blood glucose to be conveniently and accurately measured and being economical.
Leading to the present invention, intensive and thorough research into electrochemical biosensors, conducted by the present inventors, aiming to maintain economic efficiency in the construction of the measuring device in which the production lot information thereof can be easily and accurately input into the measuring device and which removes the risk of mistakes being made by the user, thus providing an accurate measurement value, resulted in the finding that, when the production lot information is recorded in the form of hue marks or hole marks on the electrochemical biosensor strip, and when various connectors are connected with a small-sized emitter-detector system to automatically read the production lot information, there is no need for a user to manually input the production lot information of a biosensor, and thus accurate measurement values can be conveniently obtained.